Conference Highlights From the 2019 Gastrointestinal and Genitourinary Cancers Symposiums
THIS YEAR saw a huge turnout and a large number of scientific abstracts presented at both the 2019 Gastrointestinal (GI) Cancers Symposium, held on January 17–19, and the 2019 Genitourinary (GU) Cancers Symposium, held on February 14–16, both in San Francisco. The GU Cancers Symposium attracted about 4,400 attendees, and 765 abstracts were submitted for presentation, while more than 3,500 people attended the GI Cancers Symposium, where nearly 800 abstracts were submitted. Each meeting featured a diverse array of groundbreaking research and novel approaches in the treatment of these cancers, and in some cases, even altering standard of care. Here we present a compilation of some of the notable studies presented during the two meetings as reported in The ASCO Post.
Sumanta Pal, MD, Guest Editor
Genitourinary Cancers Symposium
Advanced Renal Cell Carcinoma
Two phase III studies, KEYNOTE-426, which evaluated a combination regimen of pembrolizumab and axitinib vs sunitinib alone in first-line therapy for advanced renal cell carcinoma, and JAVELIN Renal 101, which compared avelumab and axitinib vs sunitinib alone in the first-line treatment of metastatic renal cell carcinoma, have confirmed the benefit of combining an immune checkpoint inhibitor with a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor, axitinib, in these settings.
In the global, open-label phase III KEYNOTE-426 study, 861 patients with previously untreated, advanced clear cell renal cell carcinoma were randomly assigned to receive pembrolizumab plus axitinib, or the multitargeted tyrosine kinase inhibitor (TKI) sunitinib. Patients continued on the therapy until disease progression or a complete response was achieved.
After a median follow-up of 12.8 months, the combination of pembrolizumab and axitinib significantly improved overall and progression-free survival compared with sunitinib alone. Objective response rates were also higher in the group receiving pembrolizumab plus axitinib vs the group receiving sunitinib monotherapy.1,2
The JAVELIN Renal 101 study is the first clinical trial to combine a programmed cell death ligand 1 (PD-L1) inhibitor, avelumab, with axitinib vs monotherapy sunitinib in the first-line setting of patients with metastatic renal cell carcinoma. In this study, 886 patients with previously untreated renal cell carcinoma were randomly assigned to receive the avelumab/axitinib combination or sunitinib alone.
The study results show that the combination therapy significantly improved median progression-free survival—13.8 months with avelumab plus axitinib vs 8.4 months with sunitinib alone—and doubled the objective response rate— 55.2% vs 25.5%, respectively.
A subgroup analysis of JAVELIN Renal 101 found that all subgroups of patients, including those with favorable-, intermediate-, and poor-risk disease, benefited from the combination treatment.3
Results From the METEOR Trial
Previous reporting of results from the phase III METEOR clinical trial, which evaluated the effectiveness of the multitargeted TKI cabozantinib vs the inhibitor of mammalian target of rapamycin (mTOR) everolimus in previously treated patients with advanced-stage renal cell carcinoma, found that the patients receiving cabozantinib experienced greater overall survival, progression-free survival, and objective response rates than patients receiving everolimus.4
In a follow-up retrospective analysis of the METEOR study, which evaluated median overall survival and whether early tumor shrinkage following treatment with either cabozantinib or everolimus could be an early indicator of prognosis, the researchers found that patients receiving cabozantinib experienced greater degrees of tumor shrinkage compared to patients receiving everolimus. In the analysis, early tumor shrinkage was associated with prolonged overall survival in patients treated with cabozantinib.5
2019 Genitourinary Cancers Symposium: Poster walk. Photo by © ASH/Todd Buchanan 2019.
Novel Approaches in the Treatment of Urothelial Carcinoma
Several studies presented at the GU Cancers Symposium utilized novel therapeutic approaches in heavily pretreated patients with urothelial carcinoma to address their unmet needs and improve their care. In a small phase I/II trial investigating single-agent treatment with sacituzumab govitecan, a novel antibody-drug conjugate of the humanized anti–Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan, researchers found that the agent is active in patients with metastatic urothelial cancer who were previously treated with chemotherapy or a checkpoint inhibitor.
The overall response rate among the 45 heavily pretreated patients enrolled in the study was 31%, which persisted in half of the responders for at least 12 months.6 Overall, the median progression-free survival was 7.3 months, and the median overall survival was 16.3 months. In addition, sacituzumab govitecan was reasonably tolerated, with few patients discontinuing the treatment due to adverse events and none stopping therapy due to neutropenia.
Androgen Receptor Inhibitor Shows Benefit in Prostate Cancer
Several studies presented during the GU Cancers Symposium show the progress researchers are making in both castration-sensitive prostate cancer and in castration-resistant prostate cancer. For example, data presented from the large phase III ARAMIS clinical trial show that the investigational androgen receptor inhibitor darolutamide significantly improved metastasis-free survival in men with high-risk nonmetastatic castration-resistant prostate cancer vs placebo, 40.4 months vs 18 months, respectively.7
In addition, grades 3 and 4 adverse events were rarely experienced by the patients receiving darolutamide, and these patients had delayed pain progression and a similar quality of life compared with patients receiving a placebo. The results suggest that darolutamide should become a new standard of care for men with high-risk nonmetastatic castration-resistant prostate cancer, according to lead author Karim Fizazi, MD, PhD, Head of the Department of Cancer Medicine at the Institut Gustave Roussy in Villejuif, France.
Gastrointestinal Cancers Symposium
Advances in Immunotherapy for the Treatment of Esophageal Cancer
Data from the global phase III KEYNOTE-181 trial support the anti–programmed cell death protein 1 (PD-1) immunotherapy pembrolizumab as a new second-line standard of care for patients with locally advanced or metastatic esophageal or gastroesophageal junction cancer who have a PD-L1 combined positive score (CPS) of 10 or greater.
In this study, 628 patients were randomly assigned to receive pembrolizumab or an investigator’s choice of paclitaxel, docetaxel, or irinotecan. Randomization was stratified by histology: squamous cell carcinoma vs adenocarcinoma and country region.
The data show that patients with PD-L1, which accounted for about 35% of the study population, had a median overall survival of 9.3 months with pembrolizumab vs 6.7 months with chemotherapy (P = .0074). The 12-month survival rate was 43% vs 20%, respectively.8
Although pembrolizumab provided a significant benefit for patients with PD-L1 CPS ≥ 10, it did not improve overall survival or progression-free survival in the overall intention-to-treat population. A trend was observed favoring pembrolizumab in patients with squamous cell carcinoma, according to lead author of the KEYNOTE-181 study Takashi Kojima, MD, of the National Cancer Center Hospital East in Kashiwa, Japan.
Making Progress in the Treatment of Hepatocellular Carcinoma
Results from two studies presented at this year’s GI Cancers Symposium show progress both in the treatment of hepatocellular carcinoma and in the quality of life for patients with the disease.
Results from the phase III CELESTIAL trial presented at the 2018 GI Cancers Symposium, and later published in The New England Journal of Medicine,9 showed that the TKI inhibitor cabozantinib improved the median overall survival in patients with hepatocellular cancer who had disease progression after at least 1 line of systemic therapy to 10.2 months vs 8 months with placebo. Based on the results from this study, the U.S. Food and Drug Administration approved cabozantinib for patients with the cancer who had been previously treated with sorafenib.
A post hoc analysis of results from the CELESTIAL study examining the impact of cabozantinib on patients’ quality of life and presented at this year’s GI Cancers Symposium found that at 50 days postrandomization, there was a reduction in health utility reported by patients receiving cabozantinib vs placebo. In addition, at subsequent time points, patients receiving cabozantinib showed a more favorable benefit in health utility vs patients receiving placebo, and that the benefit increased over time. The agent also resulted in improved quality of life in patients as determined by the five-dimensional, five-level quality-of-life survey (EQ-5D-5L).10
Combining Immunotherapy to Boost Immune Response
In a small phase II study investigating the safety, efficacy, and tolerability of perioperative treatment with the immunotherapy nivolumab or nivolumab plus ipilimumab in patients with resectable hepatocellular carcinoma, three of eight evaluable patients had a pathologic complete response to the treatment: two patients treated with nivolumab monotherapy and one patient treated with the immunotherapy combination.
The pathologic complete response in the patient treated with nivolumab plus ipilimumab showed that clinical response correlated with an increase in CD8-positive T-cell infiltration, including an increase in two effector T-cell clusters.11
The treatment was deemed safe, according to the study researchers, and surgical resection was not delayed. The study is ongoing, and the results may contribute to a paradigm shift in the perioperative treatment of hepatocellular carcinoma, concluded the investigators.
Potential New Standard of Care for Resectable Pancreatic Cancer
Several studies presented at this year’s GI Symposium evaluated the benefits of neoadjuvant treatment in patients with pancreatic cancer and in patients whose disease was fully resectable, not just “borderline” resectable. Neoadjuvant chemotherapy may be beneficial for patients in a number of ways, including early treatment of their disease, assessment of responsiveness to chemotherapy, downstaging of nodal disease, improved operability, and greater achievement of negative surgical margins.
A consensus from the studies presented is that a trend may be emerging toward a statistically significant advantage with neoadjuvant therapy.12-14
The complete results of the studies from the GU Cancers Symposium and GI Cancers Symposium highlighted here appear on the following pages. ■
DISCLOSURE: Dr. Pal is a consultant for Pfizer, Novartis, Aveo, Myriad, Genentech Exelixis, Bristol-Myers Squibb, Astellas Pharma, Ipsen, and Eisai.
1. Powles T, Plimack ER, Stus V, et al: Pembroliumab plus axitinib vs sunitinib as first-line therapy for advanced renal cell carcinoma: Phase III KEYNOTE-426 study. 2019 Genitourinary Cancers Symposium. Abstract 543. Presented February 16, 2019.
2. Rini B, Plimack E, Stus V, et al: Pembrolizumab plus axitinib vs sunitinib for advanced renal cell carcinoma. N Engl J Med 380:1116-1127, 2019.
3. Choueiri TK, Motzer RJ, Campbell MT, et al: Subgroup analysis from JAVELIN Renal 101: Outcomes for avelumab plus axitinib sunitinib in advanced cell renal cell carcinoma. 2019 Genitourinary Cancers Symposium. Abstract 544. Presented February 16, 2019.
4. Choueiri TK, Escudier B, Powles T, et al: Carbozantinib versus everolimus in advanced renal cell carcinoma (METEOR): Final results from a randomized, open-label, phase III trial. Lancet Oncol 17:917-927, 2016.
5. Duran I, Maroto P, SuЗrez C, et al: Analysis of overall survival based on early tumor shrinkage in the phase III METEOR study of cabozantinib versus everolimus in advanced renal cell carcinoma. 2019 Genitourinary Cancers Symposium. Abstract 550. Presented February 16, 2019.
6. Tagawa ST, Faltas BM, Lam ET, et al: Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer: Results from a phase I/II study. 2019 Genitourinary Cancers Symposium. Abstract 354. Presented February 15, 2019.
7. Fizazi K, Shore ND, Tammela TL, et a: ARAMIS: Efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC). 2019 Genitourinary Cancers Symposium. Abstract 140. Presented February 14, 2019.
8. Kojima T, Muro K, Francois E, et al: Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: The phase 3 KEYNOTE-181 study. 2019 Gastrointestinal Cancers Symposium. Abstract 2. Presented January 17, 2019.
9. Abou-Alfa GK, Meyer T, Cheng AL, et al: Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 379:54-63, 2018.
10. Abou-Alfa GK, Mollon P, Meyer T, et al: Quality-adjusted life years accrued with cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial. 2019 Gastrointestinal Cancers Symposium. Abstract 207. Presented January 18, 2019.
11. Kaseb AO, Pestana RC, Vence LM, et al: Randomized, open-label, perioperative phase II study evaluating nivolumab vs nivolumab plus ipilimumab in patients with resectable HCC. 2019 Gastrointestinal Cancers Symposium. Abstract 185. Presented January 18, 2019.
12. Unno M, Motoi F, Matsuyama Y, et al: Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). 2019 Gastrointestinal Cancers Symposium. Abstract 189. Presented on January 18, 2019.
13. Sohal D, McDonough S, Ahmad SA, et al: SWOG S1505: Initial findings on eligibility and neoadjuvant chemotherapy experience with mFOLFIRINOX versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma. 2019 Gastrointestinal Cancers Symposium. Abstract 414. Presented January 18, 2019.
14. Datta SK, Belini G, Singh M, et al: Survival outcomes between surgery with adjuvant therapy compared to neoadjuvant therapy with surgery in stage I pancreatic adenocarcinoma. Results from a large national cancer database. 2019 Gastrointestinal Cancers Symposium, Abstract 335. Presented January 18, 2019.